1. Technical Field
The present invention relates to the use of a panel of targeted therapy markers in selecting which anti-cancer treatment or therapy to use in a particular subject.
2. Background Information
Over 8,000,000 persons in the United States have been diagnosed with cancer, a leading cause of death in the United States. By 2001, cancer accounted for 22.9% of all deaths in the United States. Men in the United States have a 1 in 2 risk of developing cancer, while women in the United States have a 1 in 3 risk.
Cancer is a disease of accumulation of clonal cells due to abnormal cell proliferation. Accumulated clonal cells are generally referred to as a tumor. It is the increase in tumor cell number, and thus tumor burden, which ultimately accounts for the adverse effects on the host. The goal of most current cancer treatments is to reduce the number of tumor cells and to prevent their further accumulation. Thus, cancer treatments are targeted therapies.
For example, cancer may be treated by surgery, which involves the bulk removal of cancerous tissue. Though surgery may be effective in removing localized tumors found at certain locations such as in the breast, colon, or skin, it cannot be used in the treatment of tumors located in other areas, such as the backbone, nor can it be used in the treatment of disseminated neoplastic conditions such as leukemia.
Radiation therapy is another current method for treating cancer. Radiation therapy involves the exposure of living tissue to ionizing radiation causing death or damage to the exposed cells, including both those that are tumor cells and those that are not. Chemotherapy may also be used to treat cancer. Chemotherapy involves the use of chemical agents to disrupt cell replication or cell metabolism. It is used most often in the treatment of breast, lung, and testicular cancer. Currently there is a broad variety of therapeutic agents that may be used in the treatment of human cancer. Many, however, have debilitating adverse side effects.
Of these debilitating adverse side effects nausea and vomiting are the most common and severe. Other adverse side effects include cytopenia, infection, cachexia, mucositis in patients receiving high doses of chemotherapy with bone marrow rescue or radiation therapy; alopecia (hair loss); cutaneous complications, such as pruritis, urticaria, and angioedema; neurological complications; pulmonary and cardiac complications in patients receiving radiation or chemotherapy; and reproductive and endocrine complications. Radiation and chemotherapy-induced side effects significantly impact the quality of life of the patient and may dramatically influence patient compliance with treatment. If severe, many of these adverse effects may lead to hospitalization, or require treatment with analgesics for the treatment of pain.
Although some success has been achieved with the current methods of treating cancers, such approaches continue to be limited by a fundamental inability to accurately predict the likelihood of a clinically successful outcome. This is particularly true with regard to the sensitivity or resistance of a particular patient's tumor to a particular treatment or therapeutic agent. The inability to accurately predict the likelihood of a clinically successful outcome is problematic because of the adverse effects associated with cancer treatments and therapeutic agents.
Given the significant occurrence of cancer in the population and the severe adverse effects associated with current cancer treatments, there is a need for practical assays to predict the likelihood of individual tumor sensitivity to cancer treatment, including sensitivity to particular therapeutic agents. Such assays would permit the choice of a treatment or therapeutic agent or some combination thereof that a particular patient's cancer is likely to be sensitive to. The ability to predict clinical outcome of any given cancer treatment or therapeutic agent would enable health care givers to select treatments that will optimize the long-term treatment of a particular cancer, while avoiding the toxic effects of treatments that are ineffective. Thus, there is a need in this art for developing panels of targeted therapy markers, which will aid those of ordinary skill in the art in predicting the clinical effectiveness of anticancer treatments and therapeutic agents.
There also is a current need in the art for clinically focused microarrays that can be used both as an exploratory device in drug development and as a predictive diagnostic tool for determining which patients are most likely to benefit from a particular therapy. There is a need for a microarray platform, with proven predictive assays, that can be used and interpreted in a clinical pathology laboratory. Most microarray platforms are not designed to be highly automated and cannot be used by technologists without a high degree of skilled training.